Based on the theory of "disease of both blood and water" in Essentials from the Golden Cabinet （《金匮要略》）， and in combination with the dynamic syndrome evolution of heart failure with preserved ejection fraction （HFpEF）， this paper systematically clarifies the pathomechanism of HFpEF， characterized by yang deficiency as the root， blood stasis as the pivotal factor and water retention as the manifestation. Accordingly， the therapeutic principles have been proposed， which are warming yang and banking up original qi to consolidate the root， activating blood and unblocking collaterals to smooth the mechanism， and promoting urination and regulating pivot to remove the branch. On this basis， a compound formula structure of "one monarch， one minister and one assistant" is established， forming an integrated intervention strategy that synergistically combines the three methods of warming yang， activating blood， and promoting urination through combined classical formulas. Zhenwu Decoction （真武汤）， which warms yang and dissolves rheum， is used to consolidate the root and directly target the source of yang deficiency， serving as the monarch； Guizhi Fuling Pills （桂枝茯苓丸）， which activates blood， promotes urination and unblocks the pivot， assists in interrupting the binding of blood stasis and water retention， serving as the minister； Tingli Dazao Xiefei Decoction （葶苈大枣泻肺汤）， which regulates qi， disperses retained fluids， and eliminates the manifestation， alleviates acute water-retention symptoms， serving as the assistant. This compound formula is warming without being drying， diuretic without being drastic， and dispels stasis without consuming blood， thereby achieving the therapeutic effects of warming yang， activating blood， and promoting urination.

Histone lactylation is a recently identified post-translational modification, wherein lactate mediates the enzymatic addition of lactyl groups to lysine residues on histones. Since its discovery, extensive research has demonstrated that histone lactylation is widely present in human tissues and plays a pivotal role in regulating the transcription of specific genes. Subsequent studies have further established this modification as a widespread epigenetic mark with significant physiological implications. With advancing research, accumulating evidence confirms that lactylation at distinct histone sites elicits diverse biological effects—such as promoting cell proliferation, driving inflammatory responses, and enhancing fibrosis—all of which profoundly influence disease progression and serve as key drivers of disease onset and development. Conversely, inhibiting histone lactylation can alter disease outcomes, positioning histone lactylation as a promising therapeutic target. Moreover, studies have revealed crosstalk between histone lactylation and other post-translational modifications, such as acetylation and methylation, which collectively regulate disease progression. Notably, lactylation occurs not only on histones but also on non-histone proteins. Histone lactylation activates specific gene transcription and reshapes metabolic epigenetics, while non-histone lactylation directly modulates enzyme activity, signal transduction, and protein stability. These two facets form a synergistic network through shared lactate pools, common modifying enzyme systems, and pathway crosstalk, thereby constructing a multi-dimensional regulatory framework—namely, the “histone lactylation-metabolism hub-non-histone lactylation” axis. This architecture bridges metabolism and epigenetics, and deciphering its topological structure may provide novel targets for precise intervention in diseases driven by lactate-mediated signaling hijacking. Traditional Chinese medicine (TCM), grounded in clinical practice, has been shown to regulate histone lactylation by modulating lactate metabolism and lactylation-related enzymes, thereby influencing disease progression. Moreover, certain TCM formulations exhibit potential as alternative therapies for drug-resistant diseases, underscoring the significance of further exploring TCM-mediated regulation of histone lactylation in future therapeutic strategies. This review aims to elucidate the mechanisms underlying histone lactylation, systematically delineate the associations between site-specific histone lactylation and various diseases, present a comprehensive landscape of the “lactate-histone lactylation and functional protein lactylation” axis, and summarize the mechanistic basis and research advances in TCM-mediated regulation of histone lactylation for disease treatment. Additionally, we discuss current challenges in histone lactylation research and propose future directions, ultimately aiming to deepen understanding and broaden perspectives on the roles and therapeutic potential of histone lactylation in disease.

Objective: To explore the association between serum nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), NIMA-related kinase 7 (NEK7) and pulmonary fibrosis among patients with coal workers' pneumoconiosis, so as to provide a basis for the assessment of the degree of pulmonary fibrosis. Methods: Coal workers with pneumoconiosis hospitalized in the Second Affiliated Hospital of Xuzhou Medical University from July 2022 to July 2023 were selected by simple random sampling. Data such as age, stage of pneumoconiosis, and dust-exposure duration were collected through the hospital's electronic medical record management system. Venous blood was collected to detect the levels of serum NLRP3 and NEK7. High-resolution computed tomography (HRCT) image data of the chest were obtained through the hospital's imaging reporting system. The left and right lungs were divided into 6 pulmonary regions according to the upper, middle, and lower parts. The pulmonary fibrosis score was quantified according to the proportion of the pulmonary area occupied by HRCT manifestations of pulmonary fibrosis, including reticular shadows, pleural and interlobular septal thickening, traction bronchiectasis, and honeycombing. The association between the levels of serum NLRP3, NEK7, and pulmonary fibrosis was analyzed using a multiple linear regression model. Results: A total of 81 patients with coal workers' pneumoconiosis were included, all of whom were male, with a mean age of (71.46±11.69) years. There were 48, 28, and 5 cases in stage Ⅰ, stage Ⅱ, and stage Ⅲ of pneumoconiosis pathological staging, accounting for 59.26%, 34.57%, and 6.17%, respectively. There were 45 cases of tunneling and coal mining, accounting for 55.56%. There were 41 cases with dust exposure years of ≥30 years, accounting for 50.62%. The median serum NLRP3 and NEK7 in patients with coal workers' pneumoconiosis were 2.01 (interquartile range, 2.33) ng/mL and 0.98 (interquartile range, 0.83) ng/mL. The median score of pulmonary fibrosis was 5.00 (interquartile range, 5.50) points. After adjusting for age, stage of pneumoconiosis, type of work and dust-exposure duration, multiple linear regression analysis showed that serum NLRP3 (β'=0.649) and NEK7 (β'=0.346) were positively correlated with the pulmonary fibrosis score. Conclusion The increase in the levels of serum NLRP3 and NEK7 in patients with coal workers' pneumoconiosis is related to the increase in the degree of pulmonary fibrosis.

Objective:To investigate the predictive value of pre-infarction angina(PIA)combined with serum lipo-protein-associated phospholipase A2(Lp-PLA2)for no-reflow during primary percutaneous coronary interven-tion(PCI)in elderly patients with new-onset acute ST-segment elevation myocardial infarction(STEMI).Meth-ods:A total of 189 patients who hospitalized because of acute STEMI and underwent primary PCI within 12h in De-partment of Cardiology,Cangzhou People's Hospital between January 2018 and December 2022 were enrolled.Ac-cording to their TIMI blood flow during PCI,the patients were divided into no reflow group(n=42)and normal re-flow group(n=147).The baseline data were compared between two groups.Multivariate Logistic regression analy-sis was used to analyze the risk factors of no-reflow during PCI.The receiver operating characteristic(ROC)curve was plotted to evaluate the predictive value of PIA and Lp-PLA2 for no-reflow.Results:PI A occurred in 73 cases(38.6％),and no reflow occurred in 42 cases(22.2％)during primary PCI.Compared with patients in normal re-flow group,those in no reflow group had significant higher Lp-PLA2[(341.33±98.32)ng/ml vs.(261.95±75.21)ng/ml]and onset to reperfusion time[(7.02±1.28)h vs.(5.14±1.48)h],and significant lower incidence of PIA(23.8％ vs.42.9％)(P＜0.05 or＜0.01).Multivariate Logistic regression analysis showed that Lp-PLA2(OR=1.528,95％CI 1.028～2.030,P＜0.001),onset to reperfusion time(OR=2.602,95％CI 1.848～3.665,P＜0.001)were independent risk factors for no reflow during PCI in elderly STEMI patients,while PIA was an inde-pendent protective factor(OR=0.261,95％CI 0.101～0.671,P=0.005).The area under ROC curve of Lp-PLA2 combined PIA was 0.863(95％CI 0.806～0.909),which was significantly higher than those of Lp-PLA2[0.733(95％CI 0.664～0.794),Z=2.690,P=0.007]and PIA alone[0.609(95％CI 0.535～0.679),Z=5.657,P＜0.001].Conclusion:Pre-infarction angina has an important protective effect on no-reflow in STEMI patients.High Lp-PLA2 and absence of pre-infarction angina at admission may be good predictors of no-reflow during primary PCI in elderly patients with newly-onset acute STEMI,and it contributes to risk stratification of high risk patients.

Objective To investigate the effect of drug-eluting bead DACE(DEB-TACE)combined with systemic treatment for hepatocellular carcinoma(HCC)in different locations.Methods A total of 204 HCC patients who underwent DEB-TACE combined with systemic therapy(targeted and immunotherapy)were retrospectively collected.According to the anatomical location of HCC,86 cases with lesions located at the main trunk of portal vein(PV)or within 1 cm of the first PV branch were classified into central type group,while 118 cases with lesions located at the other areas were classified as peripheral type group.Follow-up was regularly performed after DEB-TACE until August,2024.The objective response rate(ORR)and disease control rate(DCR)at 1,3,6 and 12 months after DEB-TACE,also patients'progression-free survival(PFS)and overall survival(OS)were compared between groups.Results All patients were followed up for a median of 32.6 months,during which 164 cases died.Significant differences of ORR at 1 and 3 months after DEB-TACE(77.91％[67/86]vs.89.83％[106/118],34.88％[30/86]vs.54.24％[64/118])and DCR at 3 and 6 months after DEB-TACE(51.16％[44/86]vs.66.95％[79/118],34.88％[30/86]vs.50.00％[59/118])were found between groups(all P＜0.05).Patients'PFS(30.18[9.12,48.54]months)and OS(37.36[17.79,56.68])in peripheral type group were better than those in central type group(20.11[11.35,28.87]months and 23.24[3.11,43.47]months,x2=3.971,4.162,P=0.048,0.041).Conclusion The effect of DEB-TACE combined with systemic treatment for peripheral type HCC was better than for central type HCC.

Objective:To investigate the effect of asparagine synthetase (ASNS) knockdown on the senescence of retinal pigment epithelial (RPE) cells and its potential molecular mechanism.Methods:Human ARPE-19 RPE cells were divided into four groups: control group, short hairpin RNA targeting ASNS (shASNS) group, control+ (Janus kinase) JAK inhibitor group, and shASNS+ JAK inhibitor group, which were treated with short hairpin RNA control+ dimethyl sulfoxide (DMSO), shASNS+ DMSO, control+ JAK inhibitor and shASNS+ JAK inhibitor for 12 hours, respectively.An RPE cell senescence model was established by cell treatment with 500 μmol/L H 2O 2 for 24 hours.The mRNA and protein levels of ASNS and JAK were detected by real-time fluorescent quantitative PCR and Western blot, respectively.Reactive oxygen species (ROS) level within cells was measured using a kit.Cell cycle phase distribution and apoptosis rates were analyzed by flow cytometry.Cell viability from day 1 to day 5 of culturing was assessed via MTT assay.Senescent cell ratio was determined by β-galactosidase staining.Cellular damage was evaluated via immunofluorescence staining.Senescence-associated proteins (p16, pRb), and RPE markers (KRT18, CTNNB1, TJP1, BEST1) were quantified by Western blot. Results:Compared with the control group, mRNA and protein expression levels of ASNS and JAK were significantly reduced in the shASNS group, control+ JAK inhibitor group, and shASNS+ JAK inhibitor groups (all P<0.05).DCFH-DA staining revealed significantly lower ROS level in the shASNS group, control+ JAK inhibitor group, and shASNS+ JAK inhibitor group than in the control group (all P<0.05).Flow cytometry showed that there were more G2-phase cells and significantly reduced apoptosis rate in the shASNS group, control+ JAK inhibitor group, and shASNS+ JAK inhibitor group compared with the control group (all P<0.01).MTT assay indicated higher cell viability at all time points in the shASNS group, control+ JAK inhibitor group, and shASNS+ JAK inhibitor group compared with the control group, with statistically significant differences (all P<0.01).β-galactosidase-positive cell ratios in the shASNS, control+ JAK inhibitor, and shASNS+ JAK inhibitor groups were (42.36±1.28)%, (43.20±1.89)%, (25.97±1.13)%, respectively, which were significantly lower than (52.25±0.64)% in the control group (all P<0.001).p16 and pRb protein expression were decreased and γ-H2AX fluorescence intensity was attenuated in the shASNS group, control+ JAK inhibitor group, and shASNS+ JAK inhibitor group compared with the control group (all P<0.01).KRT18 and CTNNB1 expressions were upregulated, whereas TJP1 and BEST1 were downregulated in the shASNS group, control+ JAK inhibitor group, and shASNS+ JAK inhibitor group compared with the control group (all P<0.05).The shASNS+ JAK inhibitor group exhibited higher KRT18 and CTNNB1 expressions and lower TJP1 and BEST1 expressions than the shASNS and control+ JAK inhibitor groups (all P<0.05). Conclusions:ASNS knockdown can promote RPE cell proliferation, mitigate cellular damage, and delay senescence by suppressing the JAK pathway.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective： The aim of this study is to explore the predictive value of biparametric magnetic resonance imaging(bpMRI)for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L and establish a nomogram. Methods： The imaging data and clinical data of 363 patients undergoing radical prostatectomy and pelvic lymph node dissection in the First Affiliated Hospital of Nanjing Medical University from July 2018 to December 2023 were retrospectively analyzed. Univariate analysis and multivariate logistic regression were used to screen independent risk factors for pelvic lymph node metastasis in prostate cancer, and a nomogram of the clinical prediction model was established. Calibration curves were drawn to evaluate the accuracy of the model. Results： Multivariate logistic regression analysis showed extrocapusular extension (OR=8.08,95%CI=2.62－24.97, P<0.01), enlargement of pelvic lymph nodes (OR=4.45,95%CI=1.16－17.11,P=0.030), and biopsy ISUP grade(OR=1.97,95%CI=1.12－3.46, P=0.018)were independent risk factors for pelvic lymph node metastasis. The C-index of the prediction model was 0.834, which indicated that the model had a good prediction ability. The actual value of the model calibration curve and the prediction probability of the model fitted well, indicating that the model had a good accuracy. Further analysis of DCA curve showed that the model had good clinical application value when the risk threshold ranged from 0.05 to 0.70.Conclusion： For prostate cancer patients with PSA≤20 μg/L, bpMRI has a good predictive value for the pelvic lymph node metastasis of prostate cancer with extrocapusular extension, enlargement of pelvic lymph nodes and ISUP grade≥4.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Lymphatic Metastasis ; Retrospective Studies ; Nomograms ; Prostate-Specific Antigen/blood* ; Lymph Nodes/pathology* ; Pelvis ; Predictive Value of Tests ; Prostatectomy ; Lymph Node Excision ; Risk Factors ; Magnetic Resonance Imaging ; Logistic Models ; Middle Aged ; Aged

BACKGROUND: Non-invasive computed tomography angiography (CTA)-based fractional flow reserve (CT-FFR) could become a gatekeeper to invasive coronary angiography. Deep learning (DL)-based CT-FFR has shown promise when compared to invasive FFR. To evaluate the performance of a DL-based CT-FFR technique, DeepVessel FFR (DVFFR). METHODS: This retrospective study was designed for iScheMia Assessment based on a Retrospective, single-center Trial of CT-FFR (SMART). Patients suspected of stable coronary artery disease (CAD) and undergoing both CTA and invasive FFR examinations were consecutively selected from the Beijing Anzhen Hospital between January 1, 2016 to December 30, 2018. FFR obtained during invasive coronary angiography was used as the reference standard. DVFFR was calculated blindly using a DL-based CT-FFR approach that utilized the complete tree structure of the coronary arteries. RESULTS: Three hundred and thirty nine patients (60.5 ±10.0 years and 209 men) and 414 vessels with direct invasive FFR were included in the analysis. At per-vessel level, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of DVFFR were 94.7%, 88.6%, 90.8%, 82.7%, and 96.7%, respectively. The area under the receiver operating characteristics curve (AUC) was 0.95 for DVFFR and 0.56 for CTA-based assessment with a significant difference (P < 0.0001). At patient level, sensitivity, specificity, accuracy, PPV and NPV of DVFFR were 93.8%, 88.0%, 90.3%, 83.0%, and 95.8%, respectively. The computation for DVFFR was fast with the average time of 22.5 ± 1.9 s. CONCLUSIONS The results demonstrate that DVFFR was able to evaluate lesion hemodynamic significance accurately and effectively with improved diagnostic performance over CTA alone. Coronary artery disease (CAD) is a critical disease in which coronary artery luminal narrowing may result in myocardial ischemia. Early and effective assessment of myocardial ischemia is essential for optimal treatment planning so as to improve the quality of life and reduce medical costs.

Liver ischemia-reperfusion injury (LIRI) is a pathological process involving multiple injury factors and cell types, with different stages. Currently, protective drugs targeting a single condition are limited in efficacy, and interventions on immune cells will also be accompanied by a series of side effects. In the current bottleneck research stage, the multi-target and obvious clinical efficacy of Chinese medicine (CM) is expected to become a breakthrough point in the research and development of new drugs. In this review, we summarize the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in various stages of hepatic ischemia-reperfusion and on various types of cells. Combined with the current research progress in reducing ROS/RNS with CM, new therapies and mechanisms for the treatment of hepatic ischemia-reperfusion are discussed.
Reperfusion Injury/drug therapy* ; Reactive Oxygen Species/metabolism* ; Reactive Nitrogen Species/metabolism* ; Humans ; Liver/drug effects* ; Animals ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology*